蛋白酶的活化和bcl-2基因的表达对家兔缺血再灌注心肌细胞凋亡的影响

目的探讨半胱氨酸天冬氨酸蛋白酶-3的活化和bcl-2基因的动态表达对家兔缺血再灌注心肌细胞凋亡的影响。方法42只家兔建立心肌缺血再灌注模型,随机分为对照组(6只)和实验组(36只)。采用原位杂交、免疫组织化学技术等,观察家免缺血再灌注后半胱氨酸天冬氨酸蛋白酶-3 mRNA、bcl-2 mRNA动态表达的变化规律对心肌细胞凋亡细胞的数目影响。结果缺血再灌注损伤激发了半胱氨酸天冬氨酸蛋白酶-3的活化,促进了凋亡的发生,二者的曲线变化呈正相关(r=0．9286,P<0．001)。半胱氨酸天冬氨酸蛋白酶-3、bcl-2之间形成一种抗衡的网络调控构象,负责凋亡的促进和凋亡的抑制。半胱氨酸天冬氨酸蛋白酶-3 mRNA、bcl-2mRNA、细胞凋亡三者的表达,在交界区比梗死区更明显。结论半胱氨酸天冬氨酸蛋白酶-3 mRNA活化诱导的细胞凋亡是家兔缺血再灌注引起心肌细胞损伤的主要原因。交界区以凋亡为主要变化的动态演变,为临床治疗提供了一个时间窗。

Effects of caspase-3 activation and expression of bcl-2 genes on myocardial cell apoptosis after ischemia-reperfusion

Objective To explore the effects of caspase-3 activation and expression of the bcl-2 genes on myocardial cell apoptosis after ischemia-reperfusion. Methods Forty-two myocardial ischemia/reperfusion rabbit models were established and divided randomly into control group(6) and trial group(36) .The relation of regularity of changes in expression of caspase-3 mRNA and bcl-2 mRNA to number of apoptotic myocardiocytes was assessed by the techniques of in situ hybridization and immunohistochemistry. Results Ischemia-reperfusion injury provoked the caspase-3 activation and promoted the apoptosis, their changes correlated positively (r = 0.9286, P < 0.001) .A network of adjustment and control was formed between caspase-3 and bcl-2, which is responsible for promotion and inhibition of apoptosis. The expression of capase-3 mRNA and bcl-2 mRNA and apoptosis at the boundary area were more obvious than those at the infarct area. Conclusion The apoptosis induced by caspase-3 mRNA activation is the main reason that ischemia-reperfusion causes the myocardial cell injury. The gradual evolution of apoptosis in boundary area provides a time window for the treatment.